Mclean All

Front 1

Acute vs chronic leukemias

Back 1

Acute leukemia- predominance of very immature WBC precursors; these cells proliferate, and lack differentiation.

Chronic leukemia- Proliferation of relatively mature WBCs; often indolent; more commonly seen in adults than children

Front 2

Children leukemia breakdown

Back 2

Mostly ALL (80%)
-peaks in early life
Then AML
-goes up in later life
Then CLL
Then CML

Whites more than blacks
Males more than females

Front 3

ALL clinical manifestations

Back 3

fatigue
-anemic
pallor
-anemic
bruising, bleeding
-thrombocytopenic
fever
-neutropenic
lymphadenopathy
-lymphoblasts inflitrate nodes
hepatosplenomegaly
-lymphoblasts
mediastinal mass
-lymphoblasts in thymus
pain (musculoskeletal)
-bone marrow hyperplasia

Front 4

ALL Lab findings

Back 4

leukocytosis or leukopenia (high or low white blood cell count, respectively); may see “blasts” on the blood smear
anemia (low hemoglobin/hematocrit)
thrombocytopenia (low platelets)
may see chemical abnormalities consistent with “tumor lysis” (increased uric acid, phosphorus, potassium, creatinine)

Front 5

ALL diagnosis

Back 5

>25% lymphoblasts in bone marrow
- <5% is normal
lumbar puncture also required for evaluation of CNS disease
Morphology (L1, L2, L3 – based on FAB criteria)
cytochemical stains, e.g. Periodic acid-Schiff , myeloperoxidase, nonspecific esterase, etc. (ALL vs. AML)
immunophenotyping (“flow cytometry”) - monoclonal antibodies reacting with cell surface antigens (ALL vs. AML, T vs. B lineage)

Front 6

ALL cytogenetics: favorable vs unfavorable

Back 6

Findings associated with a favorable prognosis
-Hyperdiploidy (>50 chromosomes per leukemia cell)
-t(12;21) translocation (ETV6-RUNX1 fusion gene, aka TEL-AML1)
-Trisomies of chromosomes 4, 10, and 17
Findings associated with an unfavorable prognosis
-Hypodiploidy (<44 chromosomes per leukemia cell)
-t(4;11) translocation (MLL-AF4 fusion)
-t(9;22) translocation (BCR-ABL fusion or Philadelphia chromosome)
-Intrachromosomal amplification of chromosome 21 (“iAMP 21”)
-Early T-cell precursor ALL (subset of T-cell ALL; CD1a neg, CD8 neg, CD5 weak)

Front 7

Precursor T cell ("T cell") ALL associations

Back 7

associated with:
-Males > Females
-older age (5-12 years)
-high WBC count
-bulky adenopathy, mediastinal mass, hepatosplenomegaly
-CNS disease

Front 8

ALL emergencies

Back 8

Sepsis (infection)
Bleeding (from thrombocytopenia)
Tumor lysis syndrome (elevated uric acid, potassium, phosphorus, creatinine)
Hyperleukocytosis (very high WBC count)
Tracheal compression/SVC syndrome

Front 9

ALL Treatment - components of therapy

Back 9

1. Remission induction (~1 month)
2. Intensification (consolidation) (~6 months)
3. CNS treatment (throughout all phases)
4. Continuation (“maintenance”) (2-3 years)

Front 10

Commonly used drugs for ALL

Back 10

Steroids (prednisone, dexamethasone)
Vincristine
Asparaginase
Doxorubicin/daunorubicin (antharcyclines)
Methotrexate
Mercaptopurine
Cytarabine
Cyclophosphamide

Newer drugs
Imatinib, dasatinib
-BCR-ABL positive
Nelarabine
-T cell
Rituximab
-CD20 +
Clofarabine
-All subtypes of ALL

Front 11

ALL: CNS treatment

Back 11

Intrathecal chemotherapy (delivered by lumbar puncture (LP)) – start on first day of therapy and continue throughout treatment duration (18-20 LPs over ~3 years)
Radiation therapy (e.g. CNS positive at diagnosis or relapse, T-ALL)
-Only 5-20% patients currently get CNS radiation
-Can it be omitted for all patients?
High dose IV methotrexate - penetrates CNS

Front 12

ALL treatment

Back 12

Treatment generally lasts 2.5 - 3 years (exception is B-cell (Burkitt’s) ALL, which is treated intensively for only about 5 months)
In children, stem cell/bone marrow transplants (BMT) are reserved for refractory/relapsed disease or very high risk patients (but controversial in adults, in whom allogeneic BMT may be indicated in first remission)

Front 13

ALL cure rate

Back 13

~85%

Front 14

Pediatric ALL prognosis

Back 14

Favorable
-Age 1-10 years old
-WBC <50,000
-CNS disease absent
-chromosomes >50
-cytogenetics t(12;21)
-response to Tx rapid minimal residual disease

Unfavorable
-age <1, >10
-WBC >50,000
-CNS disease present
-# chromosomes <44
-cytogenetics t(4;11), t(9;22)
-Slow response to treatment
-black, hispanic
-obesity

Front 15

Late effects of ALL therapy

Back 15

Neurocognitive delay (CNS therapy)
Endocrinopathies (CNS therapy and steroids)
Gonadal failure/sterility (alkylating agents)
Cardiac dysfunction (antharcyclines)
Musculoskeletal disease (steroids)
Second malignancies (chemotherapy and radiation therapy)
Stroke (radiation therapy)

Front 16

Relapsed ALL

Back 16

Longer first remissions are better than shorter first remissions
In general, prognosis for relapsed ALL is 30-50%
-if long first remission - chemotherapy alone
-if short first remission - stem cell transplant
CNS, testicles (“sanctuaries”) are a relatively common sites of extramedullary relapse